Nucleic acid and corresponding protein entitled 161P2F10B useful in treatment and detection of cancer

Abstract

A gene (designated 161P2F10B) and its encoded protein are described wherein 161P2F10B exhibits tissue specific expression in normal adult tissue, it is aberrantly expressed in the cancers listed in Table I. Consequently, 161P2F10B provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 161P2F10B gene or fragment thereof, or its encoded protein or a fragment thereof, can be used to elicit a humoral or cellular immune response.

1 . A composition comprising: 
 a substance that modulates the status of 161P2F10B, or a molecule that is modulated by 161P2F10B whereby the status of a cell that expresses 161P2F10B is modulated.    
     
     
         2 . The composition of  claim 1 , further comprising a pharmaceutically acceptable carrier.  
     
     
         3 . A pharmaceutical composition that comprises the composition of  claim 1  in a human unit dose form.  
     
     
         4 . A composition of  claim 1  wherein the substance comprises an antibody or fragment thereof that specifically binds to a 161P2F10B-related protein.  
     
     
         5 . The antibody or fragment thereof of  claim 4 , which is monoclonal.  
     
     
         6 . A recombinant protein comprising an antigen-binding region of a monoclonal antibody of  claim 5 .  
     
     
         7 . The antibody or fragment thereof of  claim 4 , which is labeled with a detectable marker.  
     
     
         8 . The recombinant protein of  claim 6 , which is labeled with a detectable marker.  
     
     
         9 . The antibody fragment of an antibody of  claim 4 , which is an Fab, F(ab′)2, Fv or sFv fragment.  
     
     
         10 . The antibody of  claim 4 , which is a human antibody, a humanized antibody or a chimeric antibody.  
     
     
         11 . A non-human transgenic animal that produces an antibody of  claim 4 .  
     
     
         12 . A hybridoma that produces an antibody of  claim 5 .  
     
     
         13 . A single chain monoclonal antibody that immunospecifically binds to a 161P2F10B-related protein, and that comprises the variable domains of the heavy and light chains of a monoclonal antibody of  claim 5 .  
     
     
         14 . A vector comprising a polynucleotide that encodes a single chain monoclonal antibody of  claim 13 .  
     
     
         15 . A method of delivering a cytotoxic agent or a diagnostic agent to a cell that expresses 161P2F10B, said method comprising: 
 providing the cytotoxic agent or the diagnostic agent conjugated to an antibody or fragment thereof of  claim 4;  and,    exposing the cell to the antibody-agent or fragment-agent conjugate.    
     
     
         16 . A composition of  claim 1  wherein the substance comprises a polynucleotide that encodes an antibody or fragment thereof either of which immunospecifically binds to an 161P2F10B-related protein.  
     
     
         17 . A composition of  claim 3  wherein the substance comprises a 161P2F10B-related protein.  
     
     
         18 . The composition of  claim 17 , further comprising antigen presenting cells.  
     
     
         19 . The composition of  claim 1  wherein the substance comprises an analog of a peptide of eight, nine, ten, or eleven contiguous amino acids of FIG. 2 (SEQ ID NOS.: 743, 745).  
     
     
         20 . A composition of  claim 1  wherein the substance comprises a CTL polypeptide epitope of the amino acid sequence of FIG. 2 (SEQ ID NOS.: 743, 745), with a proviso that the epitope is not the entire amino acid sequence of FIG. 2 (SEQ ID NOS.: 743, 745).  
     
     
         21 . The composition of  claim 20  wherein the CTL epitope comprises a polypeptide selected from Tables V-XVIII, with a proviso that the epitope is not the entire amino acid sequence of FIG. 2 (SEQ ID NOS.: 743, 745).  
     
     
         22 . A composition of  claim 1  wherein the substance comprises an antibody polypeptide epitope of the amino acid sequence of FIG. 2 (SEQ ID NOS.: 743, 745), with a proviso that the epitope is not the entire amino acid sequence of FIG. 2 (SEQ ID NOS.: 743, 745).  
     
     
         23 . A composition of  claim 22  wherein the antibody epitope comprises a peptide region of at least 5 amino acids of FIG. 2 (SEQ ID NOS.: 743, 745) in any whole number increment up to 875 that includes an amino acid position selected from: an amino acid position having a value greater than 0.5 in the Hydrophilicity profile of FIG. 5, an amino acid position having a value less than 0.5 in the Hydropathicity profile of FIG. 6; an amino acid position having a value greater than 0.5 in the Percent Accessible Residues profile of FIG. 7; an amino acid position having a value greater than 0.5 in the Average Flexibility profile on FIG. 8; or an amino acid position having a value greater than 0.5 in the Beta-turn profile of FIG. 9, with a proviso that the epitope is not the entire amino acid sequence of FIG. 2 (SEQ ID NOS.: 743, 745).  
     
     
         24 . The recombinant protein of  claim 23 , which comprises murine antigen binding region residues and human constant region residues.  
     
     
         25 . A polynucleotide that encodes an analog peptide of  claim 19 .  
     
     
         26 . A composition of  claim 1  wherein the substance comprises a polynucleotide that comprises an 161P2F10B-related protein coding sequence, with a proviso that the coding sequence does not encode the entire amino acid sequence of FIG. 2 (SEQ ID NOS.: 743, 745).  
     
     
         27 . The composition of  claim 26  in human unit dose form.  
     
     
         28 . A composition of  claim 26  comprising a polynucleotide from position number 44 through number 2671 of FIG. 2 (SEQ ID NOS.: 744, 746).  
     
     
         29 . The composition of  claim 28  wherein T is substituted with U.  
     
     
         30 . A composition of  claim 32  that comprises the coding sequence for the polynucleotide of FIG. 2 (SEQ ID NOS.: 744, 746).  
     
     
         31 . The composition of  claim 30  wherein T is substituted with U.  
     
     
         32 . A composition of  claim 26  comprising a polynucleotide that encodes an 161P2F10B-related protein that is at least 90% homologous to the entire amino acid sequence shown in FIG. 2 (SEQ ID NOS.: 743, 745).  
     
     
         33 . The composition of  claim 32  wherein the polynucleotide encodes an 161P2F10B-related protein that is at least 90% identical to the entire amino acid sequence shown in FIG. 2 (SEQ ID NOS: 743, 745).  
     
     
         34 . A composition of  claim 26  wherein the substance comprises a polynucleotide that encodes at least one peptide set forth in Tables V-XVIII, with a proviso that the amino acid sequence of FIG. 2 is not encoded.  
     
     
         35 . A composition of  claim 26  comprising a polynucleotide that encodes a peptide region of at least 5 amino acids of FIG. 2 (SEQ ID NOS.: 743, 745) that includes an amino acid position selected from: an amino acid position having a value greater than 0.5 in the Hydrophilicity profile of FIG. 5, an amino acid position having a value less than 0.5 in the Hydropathicity profile of FIG. 6; an amino acid position having a value greater than 0.5 in the Percent Accessible Residues profile of FIG. 7; an amino acid position having a value greater than 0.5 in the Average Flexibility profile on FIG. 8; or an amino acid position having a value greater than 0.5 in the Beta-turn profile of FIG. 9, with a proviso that the entire amino acid sequence of FIG. 2 (SEQ ID NOS.: 743, 745) is not encoded.  
     
     
         36 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 26 .  
     
     
         37 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 28 .  
     
     
         38 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 29 .  
     
     
         39 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 30 , in human unit dose form.  
     
     
         40 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 31 .  
     
     
         41 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 32 .  
     
     
         42 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 33 .  
     
     
         43 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 34 .  
     
     
         44 . A pharmaceutical composition of  claim 1  wherein the substance comprises a ribozyme that cleaves a polynucleotide having 161P2F10B coding sequence and a physiologically acceptable carrier.  
     
     
         45 . A pharmaceutical composition of  claim 1  wherein the substance comprises a nucleic acid molecule that encodes a ribozyme that cleaves a polynucleotide having 161P2F10B coding sequence and a physiologically acceptable carrier.  
     
     
         46 . A pharmaceutical composition of  claim 1  wherein the substance comprises human T cells, wherein said T cells specifically recognize a 161P2F10B peptide sequence in the context of a particular HLA molecule.  
     
     
         47 . A method of inhibiting growth of cancer cells that expresses 161P2F10B, the method comprising: 
 administering to the cells the composition of  claim 1 .    
     
     
         48 . A method of  claim 47  of inhibiting growth of cancer cells that express 161P2F10B, the method comprising steps of: 
 administering to said cells an antibody or fragment thereof either of which specifically bind to a 161P2F10B-related protein.  
 
     
     
         49 . A method of  claim 47  of inhibiting growth of cancer cells that express 161P2F10B, the method comprising steps of: 
 administering to said cells a vector that encodes a single chain monoclonal antibody that immunospecifically binds to an 161P2F10B-related protein.  
 
     
     
         50 . A method of  claim 47  of inhibiting growth of cancer cells that express 161P2F10B, the method comprising steps of: 
 administering to said cells an 161P2F10B-related protein.  
 
     
     
         51 . A method of  claim 47  of inhibiting growth of cancer cells that express 161P2F10B, the method comprising steps of: 
 administering to said cells a vector that comprises a polynucleotide comprising a 161P2F10B-related protein coding sequence.  
 
     
     
         52 . A method of  claim 47  of inhibiting growth of cancer cells that express 161P2F10B, the method comprising steps of: 
 administering to said cells an antisense polynucleotide complementary to a polynucleotide having a 161P2F10B coding sequence.  
 
     
     
         53 . A method of  claim 47  of inhibiting growth of cancer cells that express 161P2F10B, the method comprising steps of: 
 administering to said cells a ribozyme that cleaves a polynucleotide having 161P2F10B coding sequence.  
 
     
     
         54 . A method of  claim 47  of inhibiting growth of cancer cells that express 161P2F10B and a particular HLA molecule, the method comprising steps of: 
 administering to said cells human T cells, wherein said T cells specifically recognize an 161P2F10B peptide sequence in the context of the particular HLA molecule.  
 
     
     
         55 . A method of treating a patient who bears cancer cells that express 161P2F10B, the method comprising: 
 administering to the patient the composition of  claim 1 .    
     
     
         56 . A method of  claim 55  for treating a patient who bears cancer cells that expresses 161P2F10B, the method comprising steps of: 
 administering to said patient an antibody or fragment thereof either of which specifically binds to a 161P2F10B-related protein.  
 
     
     
         57 . A method of  claim 55  for treating a patient who bears cancer cells that expresses 161P2F10B, the method comprising steps of: 
 administering to said patient a vector that encodes an antibody or fragment thereof either of which immunospecifically bind to an 161P2F10B-related protein.  
 
     
     
         58 . A method of  claim 57  for treating a patient with a cancer that expresses 161P2F10B, the method comprising steps of: 
 administering to said patient a vector that delivers a single chain monoclonal antibody coding sequence, whereby the encoded single chain antibody is expressed intracellularly within cancer cells that express 161P2F10B.  
 
     
     
         59 . A method of  claim 55  for treating a patient who bears cancer cells that express 161P2F10B, the method comprising steps of: 
 administering to said patient an 161P2F10B-related protein.  
 
     
     
         60 . A method of  claim 55  for treating a patient who bears cancer cells that express 161P2F10B, the method comprising steps of: 
 administering to said patient a vector that comprises a polynucleotide comprising a 161P2F10B-related protein coding sequence.  
 
     
     
         61 . A method of  claim 55  for treating a patient who bears cancer cells that express 161P2F10B, the method comprising steps of: 
 administering to said patient an antisense polynucleotide complementary to a polynucleotide having a 161P2F10B coding sequence.  
 
     
     
         62 . A method of  claim 55  for treating a patient who bears cancer cells that express 161P2F10B, the method comprising steps of: 
 administering to said patient a ribozyme that cleaves a polynucleotide having an 161P2F10B coding sequence.  
 
     
     
         63 . A method of  claim 55  for treating a patient who bears cancer cells that express 161P2F10B, the method comprising steps of: 
 administering to said patient a nucleic acid molecule that encodes a ribozyme that cleaves a polynucleotide having an 161P2F10B coding sequence.  
 
     
     
         64 . A method of  claim 55  for treating a patient who bears cancer cells that express 161P2F11B and a particular HLA molecule, the method comprising steps of: 
 administering to said patient human T cells, wherein said T cells specifically recognize an 161P2F10B peptide sequence in the context of the particular HLA molecule.  
 
     
     
         65 . A method of generating a mammalian immune response directed to 161P2F10B, the method comprising: 
 exposing cells of the mammal's immune system to an immunogenic portion of 
 a) an 161P2F10B-related protein and/or  
 b) a nucleotide sequence that encodes said protein,  
   whereby an immune response is generated to 161P2F10B.    
     
     
         66 . A method of inducing an immune response of  claim 65 , said method comprising: 
 providing a 161P2F10B-related protein that comprises at least one T cell or at least one B cell epitope;    contacting the epitope with a mammalian immune system T cell or B cell respectively, whereby the T cell or B cell is induced.    
     
     
         67 . The method of  claim 66  wherein the immune system cell is a B cell, whereby the induced B cell generates antibodies that specifically bind to the 161P2F10B-related protein.  
     
     
         68 . The method of  claim 66  wherein the immune system cell is a T cell that is a cytotoxic T cell (CTL), whereby the activated CTL kills an autologous cell that expresses the 161P2F10B-related protein.  
     
     
         69 . The method of  claim 66  wherein the immune system cell is a T cell that is a helper T cell (HTL), whereby the activated HTL secretes cytokines that facilitate the cytotoxic activity of a cytotoxic T cell (CTL) or the antibody producing activity of a B cell.  
     
     
         70 . An assay for detecting the presence of a 161P2F10B-related protein or polynucleotide in a biological sample from a patient who has or who is suspected of having cancer, comprising steps of: 
 contacting the sample with a substance of  claim 1  that specifically binds to the 161P2F10B-related protein or polynucleotide, respectively; and,    determining that there is a complex of the substance and 161P2F10B-related protein or the substance and 161P2F10B-related polynucleotide, respectively.    
     
     
         71 . An assay of  claim 70  for detecting the presence of a 161P2F10B-related protein in a biological sample from a patient who has or who is suspected of having cancer, comprising steps of: 
 contacting the sample with an antibody or fragment thereof either of which specifically bind to the 161P2F10B-related protein; and,  
 determining that there is a complex of the antibody or fragment thereof and 161P2F10B-related protein.  
 
     
     
         72 . The assay in accordance with  claim 70  further comprising a step of: 
 taking a sample from a patient who has or who is suspected of having cancer.  
 
     
     
         73 . The assay of  claim 70  for detecting the presence of an 161P2F10B polynucleotide in a biological sample, comprising: 
 contacting the sample with a polynucleotide probe that specifically hybridizes to the polynucleotide of FIG. 2 (SEQ ID NOS.: 744, 746); and,  
 detecting the presence of a hybridization complex formed by the hybridization of the probe with 161P2F10B polynucleotide in the sample, wherein the presence of the hybridization complex indicates the presence of 161P2F10B polynucleotide within the sample.  
 
     
     
         74 . An assay in accordance with  claim 70  for detecting the presence of 161P2F10B mRNA in a biological sample from a patient who has or who is suspected of having cancer, said method comprising: 
 producing cDNA from the sample by reverse transcription using at least one primer;  
 amplifying the cDNA so produced using 161P2F10B polynucleotides as sense and antisense primers, wherein the 161P2F10B polynucleotides used as the sense and antisense primers are capable of amplifying 161P2F10B cDNA; and  
 detecting the presence of the amplified 161P2F10B cDNA.  
 
     
     
         75 . A method for monitoring 161P2F10B gene products in a biological sample from a patient who has or who is suspected of having cancer, the method comprising: 
 determining the status of 161P2F10B gene products expressed by cells in a tissue sample from an individual;    comparing the status so determined to the status of 161P2F10B gene products in a corresponding normal sample; and,    identifying the presence of aberrant 161P2F10B gene products in the sample relative to the normal sample.    
     
     
         76 . A method of monitoring the presence of cancer in an individual comprising: performing the method of  claim 75  whereby the presence of elevated gene products 161P2F10B mRNA or 161P2F10B protein in the test sample relative to the normal tissue sample indicates the presence or status of a cancer.  
     
     
         77 . The method of  claim 76  wherein the cancer occurs in a tissue set forth in Table I.